Absorption, distribution, excretion and metabolism of a basic ether compound (R97) with antispasmodic activity]

The absorption, distribution, excretion and metabolism of 14C labelled 2-chlorophenyl-1-phenyl-3-(2 methyl-piperidino) propyl ether methyl iodide (14C-R97) were studied by means of direct measurement of radioactivity and autoradiographic technique in rats. 1) With intravenous administration, radioactivity was found in all the tissues and organs immediately after dosing, with particularly high levels in the liver, kidney, heart and lung. Five minutes after administration, the level of radioactivity in blood decreased to about 6% of the initial level, indicating the rapid absorption of radioactive material by other tissues and organs. Radioactivity was not detected in the brain and eye. Thirty minutes after administration, the concentration of radioactivity in the gastrointestinal contents was very high and a certain amount of radioactivity uptake was noted both in gastric and intestinal mucosa. Approximately 12% and 40% of radioactivity administered was excreted in the urine and feces respectively during the first 24 hours, however, the excretion of radioactivity by expiration was not determined. 2) With oral administration, radioactivity was restricted to the gastrointestinal tract. Activities in other tissues and organs were not detectable. Approximately 94% of the radioactivity administered was recovered in feces during the first 24 hours. 3) Radioactivity was not observed in either the foetus or placenta after both intravenous and oral administrations. 4) The results from autoradiographic study were in good accord with those described above.     

Efficacy and limitation of postoperative barbiturate therapy in severe head injury

Efficacy and limitation of barbiturate therapy employed as postoperative treatment for acute traumatic intracranial hematomas were studied in 20 patients. The clinical cases in this series included 15 males and 5 females with mean age of 41.8 years who all were operated on for intracranial hematomas within 3 days after injury. Glasgow Coma Scale (GCS) score was less than 7 in all instances and intracranial pressure (ICP) as well as arterial pressure was monitored postoperatively with Gaeltec and Gould transducers. Barbiturate therapy (5 mg/kg of thiopental as an initial dose and loading dose of 2-3 mg/kg/hour) was given when ICP rose above 20 mmHg and maintained for 3 days after operation. The outcome of the patients was assessed by Glasgow Outcome Scale 3 months after injury. The response of barbiturate on ICP and the changes of cerebral perfusion pressure (CPP) during the therapy in relation to the outcome were studied. Final outcome of the patients revealed 5 of good (good recovery and moderate disability), 3 of poor (severe disability and vegetative state) outcomes and 60% of mortality rate. Eleven out of 20 patients responded to barbiturate therapy and 0-20 mmHg of ICP reduction (mean reduction of 10 mmHg) was obtained in these cases. Among these cases, 2 out of 3 dead patients were older than 60 years. There were no responses of barbiturate in 7 patients to whom the therapy was started when ICP rose above 40 mmHg. No response of the therapy on ICP was also observed in the patients with GCS score of 3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noninvasive evaluation of hemispheric cerebral circulation and brain function in acute intracranial hypertension

Disturbance of the hemispheric cerebral circulation and brain dysfunction in acute intracranial hypertension were evaluated noninvasively by ultrasonic Doppler technique and multimodality evoked potentials consisting of auditory evoked brain-stem response (ABR), cortical somatosensory evoked potential (SEP) and visual evoked potential (VEP) in 36 patients with severe head injury and cerebrovascular disease. Glasgow coma scale score was less than 8 in all cases and the age ranged from 17 to 75 years (mean of 46 years). Intracranial pressure (ICP) was measured from the extradural space using Gaeltec transducer and systemic blood pressure was simultaneously recorded. Common carotid blood flow velocity (CBFV) was recorded on both sides and mean velocity (M), diastolic mean velocity (Md) and mean blood flow were calculated. The abnormalities on MEPs were graded into 4 categories. M and Md values on CBFV were significantly (p less than 0.05 and p less than 0.01) lowered on affected side (main lesion side) even when ICP was staying less than 20 mmHg comparing with control value obtained from the normal subjects (M: 19.48 +/- 3.52, Md: 15.98 +/- 2.01 cm/sec). With the increase of ICP more than 21 mmHg, CBFV on the contralateral side was also decreased and M as well as Md values were maintained at the lowered level during 21 to 60 mmHg of ICP. A significant rapid decrease of CBFV was observed at extreme intracranial hypertension more than 61 mmHg. Lowered CBFV was also noted when cerebral perfusion pressure was reduced less than 50 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical Overview of Nephrogenic Diabetes Insipidus Based on a Nationwide Survey in Japan

Background

Nephrogenic diabetes insipidus (NDI) is a rare disease whose complications include polyuria, renal dysfunction, growth disorder and mental retardation. The details of NDI’s clinical course have been unclear. To address this uncertainty, we performed a large investigation of the clinical course of NDI in Japan.

Methods

Between December 2009 and March 2011, we provided a primary questionnaire to 26,282 members of the Japan Endocrine Society, the Japanese Urological Association, the Japanese Society for Pediatric Endocrinology, the Japanese Society for Pediatric Nephrology, the Japanese Society of Nephrology, the Japanese Society of Neurology and the Japanese Society of Pediatric Urology. In addition, we provided a secondary questionnaire to 121 members who reported experience with cases of NDI. We asked about patient’s age at onset, diagnosis, complications, effect of treatment and patient’s genotype.

Results

We enrolled 173 patients with NDI in our study. Of these NDI patients, 143 were congenital and 30 were acquired. Of the 173, 73 patients (42%) experienced urologic complications. Among the 143 with congenital NDI, 20 patients (14%) had mental retardation. Patients with NDI mainly received thiazide diuretics, and some patients responded to treatment with desmopressin acetate (DDAVP). Gene analyses were performed in 87 patients (61%) with congenital NDI, revealing that 65 patients had an arginine vasopressin receptor type 2 (AVPR2) gene mutation and that 8 patients (9.2%) had an aquaporin 2 (AQP2) gene mutation. Patients with the AVPR2 mutation (D85N) generally showed a mild phenotype, and we found that DDAVP was generally an effective treatment for NDI among these patients.

Conclusion

We suggest that adequate diagnosis and treatment are the most important factors for improving prognoses. We further suggest that gene analysis should be performed for optimal treatment selection and the early detection of NDI among siblings.     

Brain metastasis of lung cancer with Eaton-Lambert syndrome--case report]

A case of brain metastasis of lung cancer with Eaton-Lambert syndrome (ELS) is reported. A 45-year-old male was admitted to the Department of Surgery in Kurume University Hospital on November 13, 1985, complaining of general fatigue. On admission, neurological examination revealed diplopia and fatigue of the extremities. The electromyogram (EMG) showed the waning phenomenon in low frequency repetitive stimulation (2Hz) and the waxing phenomenon in high frequency repetitive stimulation (10Hz, 20Hz). His clinical symptoms, radiological findings and EMG findings demonstrated lung cancer with ELS. Left pulmonary lobectomy with lymphnode dissection of the anterior mediastinum and pulmonary hilus was performed on December 4. Intraoperatively, the tumor was strongly adherent to a medium lymphnode. The patient experienced complete relief symptoms due to ELS. Histological examination disclosed a small cell carcinoma without lymphnode metastasis. He was discharged without any neurological deficits following chemotherapy on February 27, 1986. He was readmitted to the Department of Neurosurgery on August 29, 1986, because of the development of nausea and vomiting. Neurological examination demonstrated no abnormalities except for choked disc in the bilateral ocular fundi. The computed tomography scan revealed a metastatic brain tumor with a mural nodule and cyst. The tumor was totally removed on September 2. Histological examination revealed a typical appearance of small cell carcinoma. He followed a satisfactory postoperative course. He was discharged following radiation therapy on November 2, 1986, and was followed as an outpatient. He has no problem in daily life since then. Though the patient had an expanding metastatic brain tumor from lung cancer after the first operation, he experienced no symptoms due to ELS.(ABSTRACT TRUNCATED AT 250 WORDS)